Study of Deferasirox for Treatment of Transfusional Iron Overload in Myelodysplastic Patients

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT00110266
Collaborator
(none)
176
Enrollment
48
Locations
1
Arm
32.1
Actual Duration (Months)
3.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this trial is to examine the safety and efficacy of deferasirox in patients with Myelodysplastic Syndrome (MDS) and chronic iron overload from blood transfusions.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Detailed Description

Study entry requires a diagnosis of low or intermediate (INT-1) risk MDS per International Prognostic Scoring System (IPSS) criteria and serum ferritin ≥ 1000 ng/mL. Patients must have had at least 30 prior red blood cell transfusions. Deferasirox will be administered at an initial dose of 20 mg/kg orally once per day. Patient transfusion history and at least three complete blood count (CBC) values must be available for the 12 weeks prior to study registration for patients with MDS and chronic iron overload from blood transfusions.

Study Design

Study Type:
Interventional
Actual Enrollment :
176 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open Label, Safety and Tolerability Study of Deferasirox for Treatment of Transfusional Iron Overload in Low-risk and INT-1, Myelodysplastic Patients Using Serum Ferritin Monitoring
Actual Study Start Date :
Jul 25, 2005
Actual Primary Completion Date :
Mar 28, 2008
Actual Study Completion Date :
Mar 28, 2008

Arms and Interventions

ArmIntervention/Treatment
Experimental: ICL670

Evaluate the safety and tolerability of deferasirox 20 mg/kg/day over one year in patients with MDS

Drug: Deferasirox
20 mg/kg/day over one year in patients with MDS
Other Names:
  • ICL670A
  • chelator
  • desferal
  • iron chelation
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Participants Reporting Adverse Events [up to 53 Weeks]

      Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the study, whether or not considered related to the participant's participation in the study. Serious Adverse Events include adverse events that result in either of death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.

    Secondary Outcome Measures

    1. Change in Serum Ferritin From Baseline to Weeks 13, 25, 37 and 53 [From Baseline to Weeks 13, 25, 37 and 53]

      Change in levels of serum ferritin from baseline to 3, 6, 9 and 12 months (Weeks 13, 25, 37 and 53).

    2. Change in Labile Plasma Iron (LPI) [From Baseline to Weeks 13, 25, 37 and 49]

      LPI represents the component of non-transferrin bound iron and is an indicator of iron overload. The blood sample for LPI determinations was collected at Week 1 (prior to first dose) and at Weeks 13, 25, 37 and 49. LPI was calculated as 1 LPI unit = the quantity of reactive oxygen species produced by approximately 1.5 μM Fe

    3. Directly Chelatable Iron (DCI) [From Baseline to Weeks 13, 25, 37 and 49]

      The blood sample for DCI determinations were collected at Week 1 (prior to first dose) and at Weeks 13, 25, 37 and 49.

    4. Total Iron Levels [From Baseline to Weeks 13, 25, 37, 49 and 53]

      Levels of non-transferrin bound iron (NTBI) and serum iron from baseline to 3,6,9 and 12 months (Weeks 13, 25, 37 and 49) were assessed.

    5. Serum Transferrin Levels [From Baseline to Weeks 13, 25, 37, 49 and 53]

      Serum transferrin from baseline to 3, 6, 9 and 12 months of treatment (Visit Weeks 13, 25, 37 and 49) were assessed.

    6. Transferrin Saturation [From Baseline to Weeks 13, 25, 37, 49 and 53]

      Levels of transferrin saturation from baseline to 3, 6, 9 and 12 months.

    7. Transfusion Requirements [up to 1 year]

      Number of participants receiving transfusions, the summarized during the study.

    8. Frequency of Hematologic Improvement During the Study [up to 1 year]

      Hematologic responses defined by International Working Group response criteria in myelodysplasia. Hematologic Improvement (HI) responses, at least 9 weeks defined as: Erythroid response (pretreatment, <11 g/dL): Hgb increase by 1.5 g/dL; Relevant reduction units of Red blood cell (RBC) transfusions by absolute number at least 4 RBC transfusions/8 week compared with pretreatment transfusion number in previous 8 weeks; Only RBC transfusions for Hgb of 9.0 g/dL pretreatment count in RBC transfusion response evaluation; Platelet response (pretreatment,<100x10^9/L): If starting with >20x10^9/L platelets: absolute increase 30x10^9/L, Increase from baseline <20 x10^9/L to >20x10^9/L and by =/> 100%; Neutrophil response (pretreatment, <1.0x10^9/L): =/> 100% increase & absolute increase >0.5x10^9/L; Progression or relapse after HI: At least 1 of the following: =/>50% decrement from max response levels in granulocytes or platelets; Reduction in Hgb by 1.5 g/dL; or Transfusion dependence.

    9. Trough Plasma Deferasirox Concentration [At Week 13, 25, 37 and 49]

      The Pharmacokinetic (PK) parameters were assessed at Week 13, 25, 37 and 49 using Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) method.

    10. Treatment Compliance to Deferasirox [up to 1 year]

      Treatment compliance was assessed using records of study medication used, dosages administered, and intervals between visits during the study. Drug accountability was noted by the field monitor during site visits and at the completion of the trial. Participants were asked to return all unused medication at monthly visits.

    11. The Prevalence of Hereditary Hemochromatosis Gene (HFE) Gene Mutations [up to Week 13 (Month 3)]

      HFE (hemochromatosis) gene mutations in the Myelodysplastic Syndrome (MDS) population, the trial included testing for the C282Y, H63D and S65C HFE gene mutations. One blood sample was collected at Baseline (Week 1), or, if that visit was missing, the sample was taken at Week 13 (Month 3). Only one blood sample was to be taken from each participant.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Male or female patients with low or intermediate (INT-1) risk MDS

    • Patients can be EITHER naïve to iron chelation OR have had prior treatment with deferoxamine (DFO).

    • Age greater than or equal to 18 years

    • Availability of transfusion records for the 12 weeks prior to registration

    • A lifetime minimum of 30 previous packed red blood cell transfusions

    • Availability of at least three CBC values (pretransfusion) during the 12 weeks prior to registration

    • Serum Ferritin:

    For entry into the screening period, serum ferritin ≥ 1000 ng/mL on at least two occasions, at least two weeks apart, during the prior year.

    Serum ferritin ≥ 1000 ng/mL at screening via the central lab.

    • Life expectancy ≥ 6 months

    • Sexually active women must use an effective method of contraception, or must have undergone clinically documented total hysterectomy and/or oophorectomy, or tubal ligation or be postmenopausal (defined as amenorrhea for at least 12 months)

    • Able to provide written informed consent

    Exclusion Criteria:
    • Serum creatinine above the upper limit of normal

    • Alanine aminotransferase (ALT) > 500 U/L during screening

    • Clinical or laboratory evidence of active Hepatitis B or C

    • Urinary protein/creatinine ratio > 0.5 mg/mg

    • History of HIV positive test result (ELISA or Western blot)

    • Eastern Cooperative Oncology Group (ECOG) Performance Status > 2

    • Patients with uncontrolled systemic hypertension

    • Unstable cardiac disease not controlled by standard medical therapy

    • Patients with a diagnosis of or history of clinically relevant ocular toxicity related to iron chelation

    • Systemic diseases (cardiovascular, renal, hepatic, etc.) which would prevent study treatment

    • Pregnancy or breast feeding

    • Treatment with systemic investigational drug within the past 4 weeks or topical investigational drug within the past 7 days

    • Other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of study drug

    • History of non-compliance to medical regimens or patients who are considered potentially unreliable and/or not cooperative

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Univ of Alabama BirminghamBirminghamAlabamaUnited States35294
    2Mayo ClinicPhoenixArizonaUnited States85054
    3Bay Area Cancer Research GroupConcordCaliforniaUnited States94520
    4City of Hope National Medical CenterDuarteCaliforniaUnited States91010
    5Cedars-Sinai Medical Center, UCLA School of MedicineLos AngelesCaliforniaUnited States90048
    6UCLA Medical CenterLos AngelesCaliforniaUnited States90095-1678
    7UCSFSan FranciscoCaliforniaUnited States94143-0324
    8UCSFSan FranciscoCaliforniaUnited States94143
    9Rocky Mountain Cancer CentersAuroraColoradoUnited States80012
    10Mayo ClinicJacksonvilleFloridaUnited States32224
    11Emory University School of Medicine/Winship Cancer InstituteAtlantaGeorgiaUnited States30322
    12Straub Clinic and HospitalHonoluluHawaiiUnited States96813
    13Novartis Investigative SiteChicagoIllinoisUnited States60612
    14University of Chicago HospitalChicagoIllinoisUnited States60637-1470
    15University of Kansas Medical CenterKansas CityKansasUnited States66160
    16University of Kentucky College of Medicine, Markey Cancer CenterLexingtonKentuckyUnited States40536-0093
    17Cabrini Center for Cancer Care/Christus St. Frances Cabrini HospitalAlexandriaLouisianaUnited States71301
    18St. Agnes HealthCareBaltimoreMarylandUnited States21231-1000
    19Rush Cancer Institute Univ. of Massachussets Medical CenterWorcesterMassachusettsUnited States01605
    20Novartis Investigative SiteSouthfieldMichiganUnited States48075
    21Mayo ClinicRochesterMinnesotaUnited States55905
    22The Center for Cancer Care & Research (TCCCR)Saint LouisMissouriUnited States63110
    23Oncology Hematology West, PCOmahaNebraskaUnited States68124-2346
    24Dartmouth Hitchcock Medical CenterLebanonNew HampshireUnited States03756-0001
    25The Cancer Center at Hackensack UniversityHackensackNew JerseyUnited States07601
    26NMOHCAlbuquerqueNew MexicoUnited States87109
    27Roswell Park Cancer CenterBuffaloNew YorkUnited States14623
    28Rochester General Hospital/Lipson Cancer and Blood CenterRochesterNew YorkUnited States14621
    29Cancer Care of WNCAshevilleNorth CarolinaUnited States28801
    30Wake Forest UniversitComprehensive Cancer CenterWinston-SalemNorth CarolinaUnited States27157-1082
    31The Cleveland Clinic FoundationClevelandOhioUnited States44195
    32The Ohio State UniversityColumbusOhioUnited States43210
    33Novartis Investigative SitePortlandOregonUnited States97239
    34Thomas Jefferson University; Jefferson Medical College, Kimmel Cancer CenterPhiladelphiaPennsylvaniaUnited States19107
    35Western Pennsylvania Hospital Cancer InstitutePittsburghPennsylvaniaUnited States15224
    36The West Cancer ClinicMemphisTennesseeUnited States38120
    37Novartis Investigative siteNashvilleTennesseeUnited States37232
    38Baylor/The Methodist HospitalHoustonTexasUnited States77030
    39Utah Cancer SpecialistsSalt Lake CityUtahUnited States84106
    40Arlington Fairfax Hematology Oncology PCArlingtonVirginiaUnited States22205
    41Novartis Investigative SiteSpokaneWashingtonUnited States99202
    42Medical College of WisconsinMilwaukeeWisconsinUnited States53226
    43Novartis Investigative SiteVancouverBritish ColumbiaCanadaV6Z 1Y6
    44Novartis Investigative SiteHamiltonOntarioCanadaL8N 3Z5
    45Novartis Investigative SiteTorontoOntarioCanadaM4N 3M5
    46Novartis Investigative SiteTorontoOntarioCanadaM5g 2M9
    47Novartis Investigative SiteMontrealQuebecCanadaH1T 2M4
    48Novartis Investigative SiteMontrealQuebecCanadaH2L 4M1

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT00110266
    Other Study ID Numbers:
    • CICL670AUS03
    • NCT00343837
    First Posted:
    May 5, 2005
    Last Update Posted:
    Aug 16, 2021
    Last Verified:
    Jul 1, 2021
    Keywords provided by Novartis Pharmaceuticals
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment DetailsThe study was conducted at 39 centers in the United States and 6 centers in Canada
    Pre-assignment DetailA total of 176 participants enrolled in the study, of these 173 participants were treated. Three of the enrolled participants were not treated as 2 withdrew the consent and 1 died even before initiating the treatment. Of the 173 treated participants, 95 completed the study and 78 discontinued treatment prematurely.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionParticipants received Deferasirox 20 Milligrams per Kilogram per day (mg/kg/day) orally once per day (OD) for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
    Period Title: Overall Study
    STARTED173
    COMPLETED95
    NOT COMPLETED78

    Baseline Characteristics

    Arm/Group TitleDeferasirox
    Arm/Group DescriptionParticipants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
    Overall Participants173
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    69.9
    (11.45)
    Sex: Female, Male (Count of Participants)
    Female
    70
    40.5%
    Male
    103
    59.5%
    Race/Ethnicity, Customized (Count of Participants)
    Caucasian
    159
    91.9%
    Black
    4
    2.3%
    Oriental
    4
    2.3%
    Other
    6
    3.5%

    Outcome Measures

    1. Primary Outcome
    TitleNumber of Participants Reporting Adverse Events
    DescriptionAny untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the study, whether or not considered related to the participant's participation in the study. Serious Adverse Events include adverse events that result in either of death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
    Time Frameup to 53 Weeks

    Outcome Measure Data

    Analysis Population Description
    The safety population consisted of all participants who received at least 1 dose of study drug.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionParticipants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
    Measure Participants173
    Count of Participants [Participants]
    171
    98.8%
    2. Secondary Outcome
    TitleChange in Serum Ferritin From Baseline to Weeks 13, 25, 37 and 53
    DescriptionChange in levels of serum ferritin from baseline to 3, 6, 9 and 12 months (Weeks 13, 25, 37 and 53).
    Time FrameFrom Baseline to Weeks 13, 25, 37 and 53

    Outcome Measure Data

    Analysis Population Description
    The Full Analysis Set (FAS) populations consisted of all participants who received at least 1 dose of study drug.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionParticipants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
    Measure Participants172
    Baseline
    2771.5
    Week 13
    -146.5
    Week 25
    -167.5
    Week 37
    -505.0
    Week 53
    -592.0
    3. Secondary Outcome
    TitleChange in Labile Plasma Iron (LPI)
    DescriptionLPI represents the component of non-transferrin bound iron and is an indicator of iron overload. The blood sample for LPI determinations was collected at Week 1 (prior to first dose) and at Weeks 13, 25, 37 and 49. LPI was calculated as 1 LPI unit = the quantity of reactive oxygen species produced by approximately 1.5 μM Fe
    Time FrameFrom Baseline to Weeks 13, 25, 37 and 49

    Outcome Measure Data

    Analysis Population Description
    The full analysis set populations consisted of all participants who received at least 1 dose of study drug.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionParticipants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
    Measure Participants173
    Baseline
    0.30
    Week 13
    -0.10
    Week 25
    -0.20
    Week 37
    -0.30
    Week 49
    -0.45
    4. Secondary Outcome
    TitleDirectly Chelatable Iron (DCI)
    DescriptionThe blood sample for DCI determinations were collected at Week 1 (prior to first dose) and at Weeks 13, 25, 37 and 49.
    Time FrameFrom Baseline to Weeks 13, 25, 37 and 49

    Outcome Measure Data

    Analysis Population Description
    The full analysis set populations consisted of all participants who received at least 1 dose of study drug.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionParticipants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
    Measure Participants173
    Baseline
    0.00
    Week 13
    0.00
    Week 25
    0.00
    Week 37
    0.00
    Week 49
    0.00
    5. Secondary Outcome
    TitleTotal Iron Levels
    DescriptionLevels of non-transferrin bound iron (NTBI) and serum iron from baseline to 3,6,9 and 12 months (Weeks 13, 25, 37 and 49) were assessed.
    Time FrameFrom Baseline to Weeks 13, 25, 37, 49 and 53

    Outcome Measure Data

    Analysis Population Description
    The full analysis set populations consisted of all participants who received at least 1 dose of study drug.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionParticipants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
    Measure Participants173
    Baseline
    194.0
    Week 13
    230.50
    Week 25
    222.0
    Week 37
    212.0
    Week 49
    218.0
    Week 53
    221.00
    6. Secondary Outcome
    TitleSerum Transferrin Levels
    DescriptionSerum transferrin from baseline to 3, 6, 9 and 12 months of treatment (Visit Weeks 13, 25, 37 and 49) were assessed.
    Time FrameFrom Baseline to Weeks 13, 25, 37, 49 and 53

    Outcome Measure Data

    Analysis Population Description
    The full analysis set populations consisted of all participants who received at least 1 dose of study drug.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionParticipants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
    Measure Participants173
    Baseline
    156.0
    Week 13
    161.0
    Week 25
    160.0
    Week 37
    158.0
    Week 49
    160.0
    Week 53
    161.00
    7. Secondary Outcome
    TitleTransferrin Saturation
    DescriptionLevels of transferrin saturation from baseline to 3, 6, 9 and 12 months.
    Time FrameFrom Baseline to Weeks 13, 25, 37, 49 and 53

    Outcome Measure Data

    Analysis Population Description
    The full analysis set populations consisted of all participants who received at least 1 dose of study drug.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionParticipants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
    Measure Participants173
    Baseline
    91.00
    Week 13
    -11.00
    Week 25
    -11.00
    Week 37
    -12.50
    Week 49
    -12.00
    Week 53
    -18.00
    8. Secondary Outcome
    TitleTransfusion Requirements
    DescriptionNumber of participants receiving transfusions, the summarized during the study.
    Time Frameup to 1 year

    Outcome Measure Data

    Analysis Population Description
    The full analysis set populations consisted of all participants who received at least 1 dose of study drug.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionParticipants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
    Measure Participants173
    Screening
    163
    94.2%
    Week 1 through 13
    136
    78.6%
    Week 14 through 26
    119
    68.8%
    Week 27 through 39
    98
    56.6%
    Week 40 through 52
    72
    41.6%
    9. Secondary Outcome
    TitleFrequency of Hematologic Improvement During the Study
    DescriptionHematologic responses defined by International Working Group response criteria in myelodysplasia. Hematologic Improvement (HI) responses, at least 9 weeks defined as: Erythroid response (pretreatment, <11 g/dL): Hgb increase by 1.5 g/dL; Relevant reduction units of Red blood cell (RBC) transfusions by absolute number at least 4 RBC transfusions/8 week compared with pretreatment transfusion number in previous 8 weeks; Only RBC transfusions for Hgb of 9.0 g/dL pretreatment count in RBC transfusion response evaluation; Platelet response (pretreatment,<100x10^9/L): If starting with >20x10^9/L platelets: absolute increase 30x10^9/L, Increase from baseline <20 x10^9/L to >20x10^9/L and by =/> 100%; Neutrophil response (pretreatment, <1.0x10^9/L): =/> 100% increase & absolute increase >0.5x10^9/L; Progression or relapse after HI: At least 1 of the following: =/>50% decrement from max response levels in granulocytes or platelets; Reduction in Hgb by 1.5 g/dL; or Transfusion dependence.
    Time Frameup to 1 year

    Outcome Measure Data

    Analysis Population Description
    The analysis was performed on Per protocol population defined as number of participants who did not present any major deviations from protocol and received at least one dose of study drug.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionParticipants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
    Measure Participants91
    Response (Yes)
    7
    4%
    Response (No)
    74
    42.8%
    Missing
    10
    5.8%
    10. Secondary Outcome
    TitleTrough Plasma Deferasirox Concentration
    DescriptionThe Pharmacokinetic (PK) parameters were assessed at Week 13, 25, 37 and 49 using Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) method.
    Time FrameAt Week 13, 25, 37 and 49

    Outcome Measure Data

    Analysis Population Description
    The full analysis set populations consisted of all participants who received at least 1 dose of study drug.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionParticipants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
    Measure Participants173
    Week 13
    21.200
    Week 25
    26.700
    Week 37
    25.200
    Week 49
    30.700
    11. Secondary Outcome
    TitleTreatment Compliance to Deferasirox
    DescriptionTreatment compliance was assessed using records of study medication used, dosages administered, and intervals between visits during the study. Drug accountability was noted by the field monitor during site visits and at the completion of the trial. Participants were asked to return all unused medication at monthly visits.
    Time Frameup to 1 year

    Outcome Measure Data

    Analysis Population Description
    The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionParticipants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
    Measure Participants173
    20 to < 40 %
    2
    1.2%
    40 - < 60 %
    1
    0.6%
    60 - < 80 %
    4
    2.3%
    80 - < 100 %
    89
    51.4%
    100 - < 120 %
    65
    37.6%
    ≥ 120 %
    12
    6.9%
    12. Secondary Outcome
    TitleThe Prevalence of Hereditary Hemochromatosis Gene (HFE) Gene Mutations
    DescriptionHFE (hemochromatosis) gene mutations in the Myelodysplastic Syndrome (MDS) population, the trial included testing for the C282Y, H63D and S65C HFE gene mutations. One blood sample was collected at Baseline (Week 1), or, if that visit was missing, the sample was taken at Week 13 (Month 3). Only one blood sample was to be taken from each participant.
    Time Frameup to Week 13 (Month 3)

    Outcome Measure Data

    Analysis Population Description
    The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionParticipants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
    Measure Participants94
    Negative
    85
    49.1%
    Positive Heterozygous
    9
    5.2%
    Negative
    70
    40.5%
    Positive Heterozygous
    24
    13.9%
    Negative
    92
    53.2%
    Positive Heterozygous
    2
    1.2%

    Adverse Events

    Time FrameAll Adverse Event Were Collected From Start of Treatment up to 53 Weeks
    Adverse Event Reporting Description Out of 176 participants enrolled in the study, 173 participants received study medication. As, two participants withdrew consent and one died before initiating the treatment, were not considered for this analysis. The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
    Arm/Group TitleDeferasiroxEnrolled, Not Treated
    Arm/Group DescriptionParticipants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.Participant died before initiating the treatment.
    All Cause Mortality
    DeferasiroxEnrolled, Not Treated
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total17/173 (9.8%) 1/3 (33.3%)
    Serious Adverse Events
    DeferasiroxEnrolled, Not Treated
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total78/173 (45.1%) 0/3 (0%)
    Blood and lymphatic system disorders
    Anaemia4/173 (2.3%) 0/3 (0%)
    Febrile neutropenia7/173 (4%) 0/3 (0%)
    Haemolytic anaemia1/173 (0.6%) 0/3 (0%)
    Neutropenia1/173 (0.6%) 0/3 (0%)
    Splenic infarction1/173 (0.6%) 0/3 (0%)
    Thrombocytopenia4/173 (2.3%) 0/3 (0%)
    Cardiac disorders
    Atrial fibrillation1/173 (0.6%) 0/3 (0%)
    Atrial flutter1/173 (0.6%) 0/3 (0%)
    Cardiac arrest1/173 (0.6%) 0/3 (0%)
    Cardiac failure congestive4/173 (2.3%) 0/3 (0%)
    Cardio-respiratory arrest2/173 (1.2%) 0/3 (0%)
    Cardiomyopathy1/173 (0.6%) 0/3 (0%)
    Myocardial infarction1/173 (0.6%) 0/3 (0%)
    Pericardial effusion1/173 (0.6%) 0/3 (0%)
    Ventricular tachycardia1/173 (0.6%) 0/3 (0%)
    Eye disorders
    Blindness1/173 (0.6%) 0/3 (0%)
    Eyelid oedema1/173 (0.6%) 0/3 (0%)
    Vision blurred1/173 (0.6%) 0/3 (0%)
    Gastrointestinal disorders
    Abdominal pain1/173 (0.6%) 0/3 (0%)
    Abdominal pain upper1/173 (0.6%) 0/3 (0%)
    Constipation1/173 (0.6%) 0/3 (0%)
    Diarrhoea5/173 (2.9%) 0/3 (0%)
    Dysphagia1/173 (0.6%) 0/3 (0%)
    Gastrointestinal haemorrhage3/173 (1.7%) 0/3 (0%)
    Ileus1/173 (0.6%) 0/3 (0%)
    Intestinal perforation1/173 (0.6%) 0/3 (0%)
    Nausea3/173 (1.7%) 0/3 (0%)
    Rectal haemorrhage1/173 (0.6%) 0/3 (0%)
    Vomiting3/173 (1.7%) 0/3 (0%)
    General disorders
    Asthenia1/173 (0.6%) 0/3 (0%)
    Chest pain2/173 (1.2%) 0/3 (0%)
    Concomitant disease progression3/173 (1.7%) 0/3 (0%)
    Fatigue1/173 (0.6%) 0/3 (0%)
    Induration1/173 (0.6%) 0/3 (0%)
    Malaise1/173 (0.6%) 0/3 (0%)
    Multi-organ failure1/173 (0.6%) 0/3 (0%)
    Oedema peripheral5/173 (2.9%) 0/3 (0%)
    Pyrexia7/173 (4%) 0/3 (0%)
    Hepatobiliary disorders
    Cholecystitis1/173 (0.6%) 0/3 (0%)
    Cholecystitis acute1/173 (0.6%) 0/3 (0%)
    Hyperbilirubinaemia1/173 (0.6%) 0/3 (0%)
    Jaundice cholestatic1/173 (0.6%) 0/3 (0%)
    Immune system disorders
    Drug hypersensitivity2/173 (1.2%) 0/3 (0%)
    Infections and infestations
    Bacteraemia2/173 (1.2%) 0/3 (0%)
    Bacterial sepsis1/173 (0.6%) 0/3 (0%)
    Cellulitis6/173 (3.5%) 0/3 (0%)
    Cholecystitis infective1/173 (0.6%) 0/3 (0%)
    Clostridial infection2/173 (1.2%) 0/3 (0%)
    Clostridium bacteraemia1/173 (0.6%) 0/3 (0%)
    Escherichia sepsis1/173 (0.6%) 0/3 (0%)
    Liver abscess1/173 (0.6%) 0/3 (0%)
    Lobar pneumonia2/173 (1.2%) 0/3 (0%)
    Pharyngeal abscess1/173 (0.6%) 0/3 (0%)
    Pneumonia12/173 (6.9%) 0/3 (0%)
    Propionibacterium infection1/173 (0.6%) 0/3 (0%)
    Pseudomonal bacteraemia1/173 (0.6%) 0/3 (0%)
    Sepsis3/173 (1.7%) 0/3 (0%)
    Septic shock2/173 (1.2%) 0/3 (0%)
    Staphylococcal abscess1/173 (0.6%) 0/3 (0%)
    Staphylococcal infection1/173 (0.6%) 0/3 (0%)
    Urinary tract infection5/173 (2.9%) 0/3 (0%)
    Urinary tract infection enterococcal1/173 (0.6%) 0/3 (0%)
    Urosepsis1/173 (0.6%) 0/3 (0%)
    Wound infection staphylococcal1/173 (0.6%) 0/3 (0%)
    Injury, poisoning and procedural complications
    Femur fracture1/173 (0.6%) 0/3 (0%)
    Hip fracture4/173 (2.3%) 0/3 (0%)
    Post procedural haemorrhage1/173 (0.6%) 0/3 (0%)
    Spinal compression fracture1/173 (0.6%) 0/3 (0%)
    Subdural haematoma2/173 (1.2%) 0/3 (0%)
    Transfusion reaction1/173 (0.6%) 0/3 (0%)
    Metabolism and nutrition disorders
    Anorexia1/173 (0.6%) 0/3 (0%)
    Dehydration5/173 (2.9%) 0/3 (0%)
    Fluid overload1/173 (0.6%) 0/3 (0%)
    Haemochromatosis1/173 (0.6%) 0/3 (0%)
    Hypercalcaemia1/173 (0.6%) 0/3 (0%)
    Hypoglycaemia1/173 (0.6%) 0/3 (0%)
    Hyponatraemia1/173 (0.6%) 0/3 (0%)
    Musculoskeletal and connective tissue disorders
    Chondrocalcinosis pyrophosphate1/173 (0.6%) 0/3 (0%)
    Costochondritis1/173 (0.6%) 0/3 (0%)
    Flank pain2/173 (1.2%) 0/3 (0%)
    Muscular weakness1/173 (0.6%) 0/3 (0%)
    Pain in extremity1/173 (0.6%) 0/3 (0%)
    Tendonitis1/173 (0.6%) 0/3 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia2/173 (1.2%) 0/3 (0%)
    Chronic myelomonocytic leukaemia1/173 (0.6%) 0/3 (0%)
    Gastric cancer1/173 (0.6%) 0/3 (0%)
    Malignant melanoma1/173 (0.6%) 0/3 (0%)
    Myelodysplastic syndrome1/173 (0.6%) 0/3 (0%)
    Nervous system disorders
    Convulsion1/173 (0.6%) 0/3 (0%)
    Dizziness2/173 (1.2%) 0/3 (0%)
    Haemorrhage intracranial1/173 (0.6%) 0/3 (0%)
    Presyncope1/173 (0.6%) 0/3 (0%)
    Syncope1/173 (0.6%) 0/3 (0%)
    Transient ischaemic attack1/173 (0.6%) 0/3 (0%)
    Psychiatric disorders
    Confusional state1/173 (0.6%) 0/3 (0%)
    Renal and urinary disorders
    Acute prerenal failure1/173 (0.6%) 0/3 (0%)
    Dysuria1/173 (0.6%) 0/3 (0%)
    Haematuria1/173 (0.6%) 0/3 (0%)
    Renal failure acute6/173 (3.5%) 0/3 (0%)
    Renal impairment1/173 (0.6%) 0/3 (0%)
    Reproductive system and breast disorders
    Prostatic haemorrhage1/173 (0.6%) 0/3 (0%)
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease1/173 (0.6%) 0/3 (0%)
    Cough1/173 (0.6%) 0/3 (0%)
    Dyspnoea4/173 (2.3%) 0/3 (0%)
    Dyspnoea at rest1/173 (0.6%) 0/3 (0%)
    Dyspnoea exertional1/173 (0.6%) 0/3 (0%)
    Hypoxia2/173 (1.2%) 0/3 (0%)
    Lung infiltration2/173 (1.2%) 0/3 (0%)
    Pleural effusion1/173 (0.6%) 0/3 (0%)
    Pulmonary congestion1/173 (0.6%) 0/3 (0%)
    Pulmonary embolism1/173 (0.6%) 0/3 (0%)
    Pulmonary oedema1/173 (0.6%) 0/3 (0%)
    Respiratory distress1/173 (0.6%) 0/3 (0%)
    Respiratory failure3/173 (1.7%) 0/3 (0%)
    Skin and subcutaneous tissue disorders
    Rash macular1/173 (0.6%) 0/3 (0%)
    Rash papular1/173 (0.6%) 0/3 (0%)
    Rash pruritic1/173 (0.6%) 0/3 (0%)
    Urticaria1/173 (0.6%) 0/3 (0%)
    Vascular disorders
    Aneurysm1/173 (0.6%) 0/3 (0%)
    Deep vein thrombosis1/173 (0.6%) 0/3 (0%)
    Haemorrhage1/173 (0.6%) 0/3 (0%)
    Lymphorrhoea1/173 (0.6%) 0/3 (0%)
    Peripheral vascular disorder1/173 (0.6%) 0/3 (0%)
    Other (Not Including Serious) Adverse Events
    DeferasiroxEnrolled, Not Treated
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total166/173 (96%) 0/3 (0%)
    Blood and lymphatic system disorders
    Anaemia4/173 (2.3%) 0/3 (0%)
    Neutropenia9/173 (5.2%) 0/3 (0%)
    Splenomegaly7/173 (4%) 0/3 (0%)
    Thrombocytopenia9/173 (5.2%) 0/3 (0%)
    Cardiac disorders
    Tachycardia4/173 (2.3%) 0/3 (0%)
    Eye disorders
    Vision blurred9/173 (5.2%) 0/3 (0%)
    Gastrointestinal disorders
    Abdominal distension16/173 (9.2%) 0/3 (0%)
    Abdominal pain18/173 (10.4%) 0/3 (0%)
    Abdominal pain upper10/173 (5.8%) 0/3 (0%)
    Constipation30/173 (17.3%) 0/3 (0%)
    Diarrhoea101/173 (58.4%) 0/3 (0%)
    Dyspepsia17/173 (9.8%) 0/3 (0%)
    Flatulence6/173 (3.5%) 0/3 (0%)
    Gastrooesophageal reflux disease4/173 (2.3%) 0/3 (0%)
    Haemorrhoids5/173 (2.9%) 0/3 (0%)
    Nausea60/173 (34.7%) 0/3 (0%)
    Stomach discomfort4/173 (2.3%) 0/3 (0%)
    Stomatitis12/173 (6.9%) 0/3 (0%)
    Vomiting21/173 (12.1%) 0/3 (0%)
    General disorders
    Asthenia12/173 (6.9%) 0/3 (0%)
    Chest discomfort8/173 (4.6%) 0/3 (0%)
    Chest pain9/173 (5.2%) 0/3 (0%)
    Chills8/173 (4.6%) 0/3 (0%)
    Fatigue68/173 (39.3%) 0/3 (0%)
    Gait disturbance5/173 (2.9%) 0/3 (0%)
    Oedema6/173 (3.5%) 0/3 (0%)
    Oedema peripheral35/173 (20.2%) 0/3 (0%)
    Pain9/173 (5.2%) 0/3 (0%)
    Pyrexia28/173 (16.2%) 0/3 (0%)
    Infections and infestations
    Bronchitis4/173 (2.3%) 0/3 (0%)
    Cellulitis4/173 (2.3%) 0/3 (0%)
    Cystitis5/173 (2.9%) 0/3 (0%)
    Infection4/173 (2.3%) 0/3 (0%)
    Nasopharyngitis16/173 (9.2%) 0/3 (0%)
    Pneumonia9/173 (5.2%) 0/3 (0%)
    Sinusitis9/173 (5.2%) 0/3 (0%)
    Upper respiratory tract infection19/173 (11%) 0/3 (0%)
    Urinary tract infection17/173 (9.8%) 0/3 (0%)
    Injury, poisoning and procedural complications
    Contusion14/173 (8.1%) 0/3 (0%)
    Fall4/173 (2.3%) 0/3 (0%)
    Transfusion reaction5/173 (2.9%) 0/3 (0%)
    Investigations
    Alanine aminotransferase increased4/173 (2.3%) 0/3 (0%)
    Blood creatinine increased34/173 (19.7%) 0/3 (0%)
    Blood urea increased4/173 (2.3%) 0/3 (0%)
    International normalised ratio increased4/173 (2.3%) 0/3 (0%)
    Weight decreased12/173 (6.9%) 0/3 (0%)
    Metabolism and nutrition disorders
    Anorexia24/173 (13.9%) 0/3 (0%)
    Decreased appetite12/173 (6.9%) 0/3 (0%)
    Dehydration4/173 (2.3%) 0/3 (0%)
    Hypokalaemia9/173 (5.2%) 0/3 (0%)
    Hypomagnesaemia4/173 (2.3%) 0/3 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia21/173 (12.1%) 0/3 (0%)
    Back pain20/173 (11.6%) 0/3 (0%)
    Bone pain5/173 (2.9%) 0/3 (0%)
    Flank pain4/173 (2.3%) 0/3 (0%)
    Muscle spasms13/173 (7.5%) 0/3 (0%)
    Muscular weakness7/173 (4%) 0/3 (0%)
    Musculoskeletal pain4/173 (2.3%) 0/3 (0%)
    Myalgia5/173 (2.9%) 0/3 (0%)
    Neck pain5/173 (2.9%) 0/3 (0%)
    Pain in extremity12/173 (6.9%) 0/3 (0%)
    Nervous system disorders
    Dizziness23/173 (13.3%) 0/3 (0%)
    Dysgeusia7/173 (4%) 0/3 (0%)
    Headache21/173 (12.1%) 0/3 (0%)
    Peripheral sensory neuropathy4/173 (2.3%) 0/3 (0%)
    Syncope5/173 (2.9%) 0/3 (0%)
    Psychiatric disorders
    Anxiety4/173 (2.3%) 0/3 (0%)
    Confusional state5/173 (2.9%) 0/3 (0%)
    Depression15/173 (8.7%) 0/3 (0%)
    Insomnia12/173 (6.9%) 0/3 (0%)
    Renal and urinary disorders
    Chromaturia4/173 (2.3%) 0/3 (0%)
    Dysuria5/173 (2.9%) 0/3 (0%)
    Haematuria7/173 (4%) 0/3 (0%)
    Nephrolithiasis7/173 (4%) 0/3 (0%)
    Pollakiuria7/173 (4%) 0/3 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough21/173 (12.1%) 0/3 (0%)
    Dyspnoea36/173 (20.8%) 0/3 (0%)
    Dyspnoea exertional6/173 (3.5%) 0/3 (0%)
    Epistaxis11/173 (6.4%) 0/3 (0%)
    Nasal congestion4/173 (2.3%) 0/3 (0%)
    Pharyngolaryngeal pain18/173 (10.4%) 0/3 (0%)
    Rhinorrhoea10/173 (5.8%) 0/3 (0%)
    Sinus congestion4/173 (2.3%) 0/3 (0%)
    Throat irritation4/173 (2.3%) 0/3 (0%)
    Skin and subcutaneous tissue disorders
    Dry skin7/173 (4%) 0/3 (0%)
    Ecchymosis9/173 (5.2%) 0/3 (0%)
    Hyperhidrosis5/173 (2.9%) 0/3 (0%)
    Night sweats8/173 (4.6%) 0/3 (0%)
    Petechiae4/173 (2.3%) 0/3 (0%)
    Pruritus11/173 (6.4%) 0/3 (0%)
    Rash32/173 (18.5%) 0/3 (0%)
    Skin ulcer4/173 (2.3%) 0/3 (0%)
    Urticaria7/173 (4%) 0/3 (0%)
    Vascular disorders
    Hypertension9/173 (5.2%) 0/3 (0%)
    Hypotension10/173 (5.8%) 0/3 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleStudy Director
    OrganizationNovartis Pharmaceuticals
    Phone862-778-8300
    EmailNovartis.email@novartis.com
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT00110266
    Other Study ID Numbers:
    • CICL670AUS03
    • NCT00343837
    First Posted:
    May 5, 2005
    Last Update Posted:
    Aug 16, 2021
    Last Verified:
    Jul 1, 2021